Objectives:Diabetic neuropathy, a microvascular complication associated with diabetes, is one of the most common forms of neuropathy. Current rodent models of type 2 diabetes are mostly transgenic which fail to mimic human type 2 diabetes and its secondary complications, including peripheral neuropathy. Our aim is to develop a non-transgenic animal model of type 2 diabetic neuropathy which closely mimics the human disease. Methods: High-fat diet (HFD; normal pellet diet + lard) and a dual dose of streptozotocin (25mg/kg) were used to induce diabetes in Sprague-Dawley rats. Developments of neuropathy in these animals were measured using behavioral parameters like tail flick latency, pain threshold using randall selitto, and gait test. Nerve conduction velocity and histopathological evaluation of sciatic nerve were also carried out. Paclitaxel treated animals served as neuropathy controls. Results: The animals developed diabetes (blood glucose >250 mg/ dl; HbA1c 11.77 ±0.14%). All the classical symptoms of painful neuropathy, reduction in tail flick latency (p<0.05), reduced vocalization threshold in randall selitto (p<0.01), gait test showing a highly negative sciatic functional index (p<0.01) and reduced nerve conduction velocity (p<0.01) were evident in HFD-STZ animals. The above response was comparable to paclitaxel-treated neuropathy controls. Histopathological evaluation of sciatic nerves showed indications of sciatic nerve damage in HFD-STZ and paclitaxeltreated animals. The above neuropathic conditions were successfully reversed upon glibenclamide treatment (10 mg/kg) in HFD-STZ treated diabetic animals. Conclusion: Hence we successfully developed a cost-efficient non-transgenic model of diabetic neuropathy which closely mimics the characteristics of the human form of the disease.
Key words: Animal model, Diabetes, Neuropathy, Glibenclamide, Rat.
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